Thursday 23 January 2014

TCF3 and TCF4 are maintainer of skin epithelial stem cells

TCF is a family of DNA binding proteins, which are participating in the overall embryo development and in particular in epithelium's   development. The member of TCF family, TCF3, works together with WNT signalling in order gastrulation to proceed.  However, it was thought that after development TCF3 remains only as marker of follicle stem cells and works only with combination with WNT-signaling pathway  during wounding, induces the epidermis to undergo de novo hair follicle morphogenesis. 

Recently the team of Dr. Nguen from the Rockefeller University Tcf3 and Tcf4 are the key transcription factors to maintain long-term epidermal homeostasis. Overall, Tcf3 and Tcf4 may be essential for establishing and maintaining all skin epithelial stem cells through Wnt-dependent and Wnt-independent roles.

Saturday 18 January 2014

Telocytes

Telocytes (TCs), a particular interstitial cell type, have been recently described in a wide variety of mammalian organs. The TCs are identified morphologically by a small cell body and extremely long (tens to hundreds of micrometer), thin prolongations (less than 100 nm in diameter, below the resolving power of light microscopy) called telopodes www.telocytes.com


Recently,  Ceafalan et al (2012) demonstrated that TCs were present in human dermis. In particular, TCs were found in the reticular dermis and  around blood vessels. Screening for antigens showed two subpopulations of dermal TCs; one of which was positive for CD34, which is hallmark of stem cells. The TCs were connected to each other by homocellular junctions, and they formed an interstitial 3D network.  Moreover, TCs established atypical heterocellular junctions with stem cells (clusters of undifferentiated cells). 

Probably, TC could be one of most significant  parts of skin regeneration's enigma.

Source:  Ceafalan et al (2012)

 
Image: telocytes.com

Bioinformatics analysis of aging microarray profiles

Changes in gene expression are associated with numerous biological processes, cellular responses and disease states. However, elucidating the transcriptional features of aging and how these relate to physiological, biochemical and pathological changes with age remains a critical problem.

Considering the number of aging gene expression studies conducted to date it is impossible to analyse them without means of bioinformatics. Because the underlying molecular mechanisms of aging remain a subject of debate,  whether independent transcriptional programs can drive aging in different tissues is unknown. Previous results suggest that most genes differentially expressed with age in a given tissue are not genes specifically expressed in that tissue, suggesting that only a small fraction of transcriptional responses are tissue-specific.

The results of article by de Magalhães et al (2009) reveal several signatures of aging most notably involving an activation of inflammation/immune response genes. The most significant gene was APOD or apolipoprotein D, previously associated with Alzheimer's diseases. In addition, numerous genes overexpressed with age play roles in inflammation, such as CTSS, FCGR2B, IGJ, C3, C1QA and C1QB. Other genes consistently overexpressed with age included lysozyme (LYZ), clusterin (CLU), microsomal glutathione S-transferase 1 (MGST1), glutathione S-transferase A1 (GSTA1), S100 calcium binding protein A4 (S100A4) and A6 (S100A6), and annexin A3 (ANXA3) and A5 (ANXA5).B and include four genes encoding mitochondrial proteins (ATP5G3, NDUFB11, UQCRQ and UQCRFS1) and three collagen genes (COL3A1, COL1A1 and COL4A5).

These differentially expressed genes may serve as a basis for further studies, for example, for deriving reliable biomarkers of aging.

Sunday 12 January 2014

Autophagy in focus

Everyone, who is interested in ageing, knows that autophagy is very important cell process, that helps to keep cell free from unnecessary or dysfunctional cellular components.

Cell research journal gives us a unique opportunity of free access to its special issue about autophagy. Enjoy!



Friday 10 January 2014

Broken heart? Let's glue it!

It is widely known that heart wounds are difficult to repair. Due to constant heart moving it is very complicated to hold wound's edges together in order to provide the contact and ability to repair the muscle. Previously threads and staples were used in such situations.  Of course, they are not a best solution, because damage of the muscle occurring during theirs usage. 

Now it seems that the era of  threads and staples is coming to the end. Scientists from Harvard Medical School created a special glue, which is able to stick together the edges of a wound and after solidification to expand and contract with the heart muscle. Thus surgeons do not need any more threads and staples! Remarkably, that the glue can be applied not only to the heart wounds, but to intestines and blood vessels too.



p16INK4A is a biomarker of skin ageing

Senescent cells  lose theirs ability to replicate mainly due to increased expression of proteins-cell cycle regulators, called cycle check point proteins. p16INK4A is one of the such proteins. Recently, a study showing a  p16IK4A as a biomarker of ageing was published in Journal of investigative dermatology. 

Dr. Adamus and colleagues showed that expression of the p16INK4A increases significantly in the basal layer of human epidermis and in dermal fibroblasts during the ageing process, confirming that p16INK4A is a biomarker of skin ageing. Also the scientists demonstrated the possibility to revert aged phenotype to a younger one and vice versa by controlling expression of the protein.

First, they induced over expression of  p16INK4A and observed a dramatic alterations in phenotype. Cultures with increased p16INK4A expression showed significant atrophy and other signs of ageing progression. 

Second, Dr. Adamus and colleagues silenced the expression of  p16INK4A, after that morphology of aged culture was improved significantly and resembled that of a much younger donor.

Thus, it was experimentally confirmed that aged skin phenotype could be improved by slowing down  the expression of p16INK4A.


Source:  Journal of investigative dermatology. 


Wednesday 8 January 2014

Broadband Light Treatment of skin aging

Dr. Chang from Stanford School of Medicine showed the unique effectiveness of  broadband light treatment on skin aging. BBL, also known as intense pulse light, is a commonly available and popular method to ‘‘rejuvenate’’ the skin. BBL uses a broad band of noncoherent light waves, ranging from 560 to 1,200, which are absorbed by different molecules in skin. According to the American Society for Aesthetic Plastic Surgery, over $215 million dollars were spent in the United States in 2009 on these procedures.

The study showed that BBL induces skin rejuvenation on molecular level, i.e., the pattern of genes' expression more closely resembles younger skin. However, the molecular changes that are induced by this treatment are still to be unclear.

Tuesday 7 January 2014

ROS and skin aging

Reactive oxygen species (ROS) is one of the by-products of cell's metabolism.  They can lead to DNA, protein and even cell's organelles damaging. 

However, cell does have a protection against ROS - robust pathways for maintaining intracellular homoeostasis. First, ROS will face with the one of the superoxide dismutases, for example, SOD2.  SOD2 is a mitochondrial matrix protein that converts the superoxide anion (O2-) to hydrogen peroxide (H2O2), which is in turn, converted to molecular oxygen and water by catalase and peroxiredoxins. 

It was shown that normal ageing in mice accompanied by impaired mitochondrial complex II activity. The similar phenotype was observed in mice with shut downed SOD2 gene: such mice exhibit significant epidermal thinning. This is caused by decreased cellular proliferation in the senescent skin tissue. 
Yet, the link between SOD2 gene and skin ageing does not seem to be direct:  heterozygous for SOD2 mice shows DNA damage andpredisposition to cancer, but without any impact on the lifespan.

Source: Aging